Outcomes Following Intraoperative Calcar Fractures During Cementless Total Hip Arthroplasty.

BACKGROUND: Intraoperative calcar fractures (IOCFs) are an established complication of cementless total hip arthroplasty (THA). Prompt recognition and management may prevent subsequent postoperative complications. This study aimed to evaluate the outcomes and revision rates of THAs with IOCFs identified and managed intraoperatively. METHODS: There were 11,438 primary cementless THAs performed at a single institution from 2009 to 2022. Prospectively collected data on cases with an IOCF was compared to cases without the complication. The fracture group had a lower body mass index (26.9 versus 28.9 kg/m2; P = .01). Patient age, sex, and mean follow-up (3.2 (0 to 12.8) versus 3.5 years (0 to 14); P = .45) were similar between groups. RESULTS: An IOCF occurred in 62 of 11,438 (0.54%) cases. The THAs done via a direct anterior approach experienced the lowest rate of fractures (31 of 7,505, 0.4%) compared to postero-lateral (27 of 3,759, 0.7%; P = .03) and lateral (4 of 165, 2.4%; P < .01) approaches. Of the IOCFs, 48 of 62 (77%) were managed with cerclage cabling, 4 of 62 (6.5%) with intraoperative stem design change and cabling, 4 of 62 (6.5%) with restricted weight-bearing, and 6 of 62 (9.7%) with no modification to the standard postoperative protocol. The IOCF group experienced one case of postoperative component subsidence. No subjects in the IOCF cohort required revision, and rates were similar between groups (0 of 62, 0% versus 215 of 11,376, 1.9%; P = .63). Postoperative Hip dysfunction and Osteoarthritis Outcome Score for Joint Replacement scores were comparable (85.7 versus 86.4; P = .80). CONCLUSIONS: Cementless THA complicated by IOCF had similar postoperative revision rates and patient-reported outcome measures at early follow-up when compared to patients not experiencing this complication. Surgeons may use these data to provide postoperative counseling on expectations and outcomes following these rare intraoperative events.

Debridement, Antibiotics, and Implant Retention in Unicompartmental Knee Arthroplasty Infection.

BACKGROUND: This multicenter study sought to further investigate the method and outcome of debridement, antibiotics, and implant retention (DAIR) for the management of unicompartmental knee periprosthetic joint infection (PJI). METHODS: This retrospective study was performed on 52 patients who underwent DAIR for PJI of a unicompartmental knee arthroplasty (UKA) across 4 academic medical centers, all performed by fellowship-trained arthroplasty surgeons. Patient demographics, American Society of Anesthesiologists score, infecting organism, operative data, antibiotic data, and success in infection control at 1 year were collected. RESULTS: The average time from index surgery to diagnosis of PJI was 11.1 weeks (range, 1.4 to 48). There was no correlation between time of diagnosis and success at 1 year (R = 0.09, P = .46). There was an association between surgical synovectomy and the eradication of infection (R = 0.28, P = .04). Overall, there was an 80.8% (42 of 52) infection-controlled success rate at 1 year from the DAIR procedure. All DAIR failures went on to require another procedure, either 1-stage (2 of 10) or 2-stage (8 of 10) revision to total knee arthroplasty (TKA). Of the DAIR successes, 6 (14.3%) went on to require conversion to TKA for progression of arthritis within 5 years. CONCLUSIONS: This study demonstrates that DAIR is a safe and moderately effective procedure in the setting of acute PJI of UKA across institutions, with a success rate consistent with DAIR for TKA. The data suggest that a wide exposure and thorough synovectomy be incorporated during the DAIR UKA to improve the likelihood of successful eradication of PJI at the 1-year mark. LEVEL OF EVIDENCE: Level III.

Outpatient Total Knee Arthroplasty From a Stand-Alone Surgery Center: Safe as the Hospital?

BACKGROUND: Literature suggests that outpatient arthroplasty may result in low rates of complications and readmissions. There is, however, a dearth of information on the relative safety of total knee arthroplasty (TKA) performed at stand-alone ambulatory surgery centers (ASCs) versus hospital outpatient (HOP) settings. We aimed to compare safety profiles and 90-day adverse events of these 2 cohorts. METHODS: Prospectively collected data were reviewed on all patients who underwent outpatient TKA from 2015 to 2022. The ASC and HOP groups were compared, and differences in demographics, complications, reoperations, revisions, readmissions, and emergency department (ED) visits within 90 days of surgery were analyzed. There were 4 surgeons who performed 4,307 TKAs during the study period, including 740 outpatient cases (ASC = 157; HOP = 583). The ASC patients were younger than HOP patients (ASC = 61 versus HOP = 65; P < .001). Body mass index and sex did not differ significantly between groups. RESULTS: Within 90 days, 44 (6%) complications occurred. No differences were observed between groups in rates of 90-day complications (ASC = 9 of 157, 5.7% versus HOP = 35 of 583, 6.0%; P = .899), reoperations (ASC = 2 of 157, 1.3% versus HOP = 3 of 583, 0.5%; P = .303), revisions (ASC = 0 of 157 versus HOP = 3 of 583, 0.5%; P = 1), readmissions (ASC = 3 of 157, 1.9% versus HOP = 8 of 583, 1.4%; P = .625), and ED visits (ASC = 1 of 157, 0.6% versus HOP = 3 of 583, 0.5%; P = .853). CONCLUSION: These results suggest that in appropriately selected patients, outpatient TKA can be safely performed in both ASC and HOP settings with similar low rates of 90-day complications, reoperations, revisions, readmissions, and ED visits.

Early Practice All-Cause Complications for Fellowship-Trained Anterior Hip Surgeons Are Not Increased When Compared to "Gold Standard" Experienced Posterior Approach Surgeons.

BACKGROUND: Increased complication rates have been reported during the learning curve for direct anterior approach (DAA) total hip arthroplasty (THA). However, emerging literature suggests that complications associated with the learning curve may be substantially reduced with fellowship training. METHODS: Our institutional database was queried to identify 2 groups: (1) 600 THAs comprised of the first 300 consecutive cases performed by 2 DAA fellowship-trained surgeons; and (2) 600 posterolateral approach (PA) THAs, including the most recent 300 primary cases performed by 2 experienced PA surgeons. All-cause complications, revision rates, reoperations, operative times, and transfusion rates were evaluated. RESULTS: Comparing DAA and PA cases, there were no significant differences in rates of all-cause complications (DAA = 18, 3.0% versus PA = 23, 3.8%; P = .43), periprosthetic fractures (DAA = 5, 0.8% versus PA = 10, 1.7%; P = .19), wound complications (DAA = 7, 1.2% versus PA = 2, 0.3%; P = .09), dislocations (DAA = 2, 0.3% versus PA = 8, 1.3%, P = .06), or revisions (DAA = 2, 0.3% versus PL = 5, 0.8%; P = .45) at 120 days postoperatively. There were 4 patients who required reoperation for wound complications, all within the DAA group (DAA = 4, 0.67% versus PA = 0; P = .045). Operative times were shorter in the DAA group (DAA <1.5 hours = 93% versus PA <1.5 hours = 86%; P < .01). No blood transfusions were given in either group. CONCLUSION: In this retrospective study, DAA THAs performed by fellowship-trained surgeons early in practice were not associated with higher complication rates compared to THAs performed by experienced PA surgeons. These results suggest that fellowship training may allow DAA surgeons to complete their learning curve period with complication rates similar to experienced PA surgeons.

Timing and Factors Associated With Revision for Infection After Primary Total Knee Arthroplasty Based on American Joint Replacement Registry Data.

BACKGROUND: Infection following total knee arthroplasty (TKA) remains a challenging clinical problem. Using American Joint Replacement Registry data, this study examined factors related to the incidence and timing of infection. METHODS: Primary TKAs performed from January 2012 through December 2018 among patients ≥65 years of age at surgery were queried from the American Joint Replacement Registry and merged with Medicare data to enhance capture of revisions for infection. Multivariate Cox regressions incorporating patient, surgical, and institutional factors were used to produce hazard ratios (HRs) associated with revision for infection and mortality after revision for infection. RESULTS: Among 525,887 TKAs, 2,821 (0.54%) were revised for infection. Men had an increased risk of revision for infection at all-time intervals (≤90 days, HR = 2.06, 95% CI: 1.75-2.43, P < .0001; >90 days to 1 year, HR = 1.90, 95% CI: 1.58-2.28, P < .0001; >1 year, HR = 1.57, 95% CI: 1.37-1.79, P < .0001). TKAs performed for osteoarthritis had an increased risk of revision for infection at ≤90 days (HR = 2.01, 95% CI: 1.45-2.78, P < .0001) but not at later times. Mortality was more likely among patients who had a Charlson Comorbidity Index (CCI) ≥ 5 compared to those who had a CCI ≤ 2 (HR = 3.21, 95% CI: 1.35-7.63, P = .008). Mortality was also more likely among older patients (HR = 1.61 for each decade, 95% CI: 1.04-2.49, P = .03). CONCLUSION: Based on primary TKAs performed in the United States, men were found to have a persistently higher risk of revision for infection, while a diagnosis of osteoarthritis was associated with a significantly higher risk only during the first 90 days after surgery.

Increased Microbial Diversity and Decreased Prevalence of Common Pathogens in the Gut Microbiomes of Wild Turkeys Compared to Domestic Turkeys.

Turkeys (Meleagris gallopavo) provide a globally important source of protein and constitute the second most important source of poultry meat in the world. Bacterial diseases are common in commercial poultry production, causing significant production losses for farmers. Due to the increasingly recognized problems associated with large-scale/indiscriminate antibiotic use in agricultural settings, poultry producers need alternative methods to control common bacterial pathogens. In this study, we compared the cecal microbiota of wild and domestic turkeys, hypothesizing that environmental pressures faced by wild birds may select for a disease-resistant microbial community. Sequence analyses of 16S rRNA genes amplified from cecal samples indicate that free-roaming wild turkeys carry a rich and variable microbiota compared to domestic turkeys raised on large-scale poultry farms. Wild turkeys also had very low levels of Staphylococcus, Salmonella, and Escherichia coli compared to domestic turkeys. E. coli strains isolated from wild and domestic turkey cecal samples also belong to distinct phylogenetic backgrounds and differ in their propensity to carry virulence genes. E. coli strains isolated from factory-raised turkeys were far more likely to carry genes for capsule (kpsII and kpsIII) or siderophore (iroN and fyuA) synthesis than were those isolated from wild turkeys. These results suggest that the microbiota of wild turkeys may provide colonization resistance against common poultry pathogens. IMPORTANCE Due to the increasingly recognized problems associated with antibiotic use in agricultural settings, poultry producers need alternative methods to control common bacterial pathogens. In this study, we compare the microbiota of wild and domestic turkeys. The results suggest that free-ranging wild turkeys carry a distinct microbiome compared to farm-raised turkeys. The microbiome of wild birds contains very low levels of poultry pathogens compared to that of farm-raised birds. The microbiomes of wild turkeys may be used to guide the development of new ways to control disease in large-scale poultry production.

Bile Salts Regulate Zinc Uptake and Capsule Synthesis in a Mastitis-Associated Extraintestinal Pathogenic Escherichia coli Strain.

Extraintestinal pathogenic Escherichia coli (ExPEC) strains are major causes of urinary and bloodstream infections. ExPEC reservoirs are not completely understood. Some mastitis-associated E. coli (MAEC) strains carry genes associated with ExPEC virulence, including metal scavenging, immune avoidance, and host attachment functions. In this study, we investigated the role of the high-affinity zinc uptake (znuABC) system in the MAEC strain M12. Elimination of znuABC moderately decreased fitness during mouse mammary gland infections. The ΔznuABC mutant strain exhibited an unexpected growth delay in the presence of bile salts, which was alleviated by the addition of excess zinc. We isolated suppressor mutants with improved growth in bile salts, several of which no longer produced the K96 capsule made by strain M12. The addition of bile salts also reduced capsule production by strain M12 and ExPEC strain CP9, suggesting that capsule synthesis may be detrimental when bile salts are present. To better understand the role of the capsule, we compared the virulence of mastitis strain M12 with that of its unencapsulated ΔkpsCS mutant in two models of ExPEC disease. The wild-type strain successfully colonized mouse bladders and kidneys and was highly virulent in intraperitoneal infections. Conversely, the ΔkpsCS mutant was unable to colonize kidneys and was unable to cause sepsis. These results demonstrate that some MAEC strains may be capable of causing human ExPEC illness. The virulence of strain M12 in these infections is dependent on its capsule. However, capsule may interfere with zinc homeostasis in the presence of bile salts while in the digestive tract.

Gqα/G11α deficiency in dorsomedial hypothalamus leads to obesity resulting from decreased energy expenditure and impaired sympathetic nerve activity.

The G-protein subunits Gqα and G11α (Gq/11α) couple receptors to phospholipase C, leading to increased intracellular calcium. In this study we investigated the consequences of Gq/11α deficiency in the dorsomedial hypothalamus (DMH), a critical site for the control of energy homeostasis. Mice with DMH-specific deletion of Gq/11α (DMHGq/11KO) were generated by stereotaxic injection of adeno-associated virus (AAV)-Cre-green fluorescent protein (GFP) into the DMH of Gqαflox/flox:G11α-/- mice. Compared with control mice that received DMH injection of AAV-GFP, DMHGq/11KO mice developed obesity associated with reduced energy expenditure without significant changes in food intake or physical activity. DMHGq/11KO mice showed no defects in the ability of the melanocortin agonist melanotan II to acutely stimulate energy expenditure or to inhibit food intake. At room temperature (22°C), DMHGq/11KO mice showed reduced sympathetic nervous system activity in brown adipose tissue (BAT) and heart, accompanied with decreased basal BAT uncoupling protein 1 (Ucp1) gene expression and lower heart rates. These mice were cold intolerant when acutely exposed to cold (6°C for 5 h) and had decreased cold-stimulated BAT Ucp1 gene expression. DMHGq/11KO mice also failed to adapt to gradually declining ambient temperatures and to develop adipocyte browning in inguinal white adipose tissue although their BAT Ucp1 was proportionally stimulated. Consistent with impaired cold-induced thermogenesis, the onset of obesity in DMHGq/11KO mice was significantly delayed when housed under thermoneutral conditions (30°C). Thus our results show that Gqα and G11α in the DMH are required for the control of energy homeostasis by stimulating energy expenditure and thermoregulation.NEW & NOTEWORTHY This paper demonstrates that signaling within the dorsomedial hypothalamus via the G proteins Gqα and G11α, which couple cell surface receptors to the stimulation of phospholipase C, is critical for regulation of energy expenditure, thermoregulation by brown adipose tissue and the induction of white adipose tissue browning.

S043 mythbuster: truncal vagotomy and gastric drainage procedures.

INTRODUCTION: You are sitting for your oral surgery board exam and the examiner asks what you do when you realize that you have accidentally cut the posterior vagus nerve during a hiatal hernia repair. Is the answer to proceed with a gastric drainage procedure correct? The prevailing dogma seems to be that inadvertent vagotomy will produce gastric stasis/paresis and the stomach will not empty and hence should be accompanied by a gastric drainage procedure. This report presents clinical outcomes of 49 patients who underwent truncal vagotomy without a drainage procedure (pyloroplasty or gastrojejunostomy). METHODS: 49 patients underwent truncal vagotomy with laparoscopic adjustable gastric banding in an IRB (Investigational Review Board)-approved clinical trial to determine if the addition of a vagotomy would increase achieved weight loss when compared to gastric banding alone. The details of this trial were presented at SAGES (Martin and Earle in Surg Endosc 25:2522-2525, 2011) in 2010. The patients in this study have been followed for over ten years and their histories were examined to look for evidence of gastric stasis or intractable diarrhea or if they required further surgery for these complaints. RESULTS: 49 patients have been followed for a mean of 10.9 years. All except one have experienced a loss of hunger and cessation of gastric borborygmus. One patient showed mild delayed gastric emptying after developing diabetes. Two other patients with DM carry a diagnosis of gastroparesis. No patient has experienced intractable diarrhea. Five patients have had revisions to sleeve gastrectomy or gastric bypass for weight loss failure or esophageal dilatation and GERD. CONCLUSIONS: Review of these truncal vagotomy patients without drainage procedures at 10 years does not support the myth that the stomach will not empty after vagotomy and a gastric drainage procedure should always accompany truncal vagotomy.

Utility of a Telephone Triage Hotline in Response to the COVID-19 Pandemic: Longitudinal Observational Study.

BACKGROUND: During the initial months of the COVID-19 pandemic, rapidly rising disease prevalence in the United States created a demand for patient-facing information exchanges that addressed questions and concerns about the disease. One approach to managing increased patient volumes during a pandemic involves the implementation of telephone-based triage systems. During a pandemic, telephone triage hotlines can be employed in innovative ways to conserve medical resources and offer useful population-level data about disease symptomatology and risk factor profiles. OBJECTIVE: The aim of this study is to describe and evaluate the COVID-19 telephone triage hotline used by a large academic medical center in the midwestern United States. METHODS: Michigan Medicine established a telephone hotline to triage inbound patient calls related to COVID-19. For calls received between March 24, 2020, and May 5, 2020, we described total call volume, data reported by callers including COVID-19 risk factors and symptomatology, and distribution of callers to triage algorithm endpoints. We also described symptomatology reported by callers who were directed to the institutional patient portal (online medical visit questionnaire). RESULTS: A total of 3929 calls (average 91 calls per day) were received by the call center during the study period. The maximum total number of daily calls peaked at 211 on March 24, 2020. Call volumes were the highest from 6 AM to 11 AM and during evening hours. Callers were most often directed to the online patient portal (1654/3929, 42%), nursing hotlines (1338/3929, 34%), or employee health services (709/3929, 18%). Cough (126/370 of callers, 34%), shortness of breath (101/370, 27%), upper respiratory infection (28/111, 25%), and fever (89/370, 24%) were the most commonly reported symptoms. Immunocompromised state (23/370, 6%) and age >65 years (18/370, 5%) were the most commonly reported risk factors. CONCLUSIONS: The triage algorithm successfully diverted low-risk patients to suitable algorithm endpoints, while directing high-risk patients onward for immediate assessment. Data collected from hotline calls also enhanced knowledge of symptoms and risk factors that typified community members, demonstrating that pandemic hotlines can aid in the clinical characterization of novel diseases.

Staphylococcus aureus metal acquisition in the mastitic mammary gland.

Mastitis, resulting from mammary gland infection, is a common and painful disease associated with lactation. In addition to the impact on human and animal health, mastitis causes substantial economic losses in the dairy industry. Staphylococcus aureus is a frequent cause of mastitis worldwide. Despite significant progress in understanding S. aureus pathogenesis in general, much remains to be learned regarding virulence factors relevant in the context of mastitis. This review outlines the molecular mechanisms by which S. aureus acquires essential metals such as iron, zinc, manganese, copper, cobalt and nickel within lactating mammary glands, while exposing areas where our current knowledge is deficient. Increased understanding of how these factors facilitate bacterial survival in the lactating mammary gland can provide therapeutic targets for more effective mastitis prevention and treatment.

The stimulatory G protein Gsα is required in melanocortin 4 receptor-expressing cells for normal energy balance, thermogenesis, and glucose metabolism.

Central melanocortin 4 receptors (MC4Rs) stimulate energy expenditure and inhibit food intake. MC4Rs activate the G protein Gsα, but whether Gsα mediates all MC4R actions has not been established. Individuals with Albright hereditary osteodystrophy (AHO), who have heterozygous Gsα-inactivating mutations, only develop obesity when the Gsα mutation is present on the maternal allele because of tissue-specific genomic imprinting. Furthermore, evidence in mice implicates Gsα imprinting within the central nervous system (CNS) in this disorder. In this study, we examined the effects of Gsα in MC4R-expressing cells on metabolic regulation. Mice with homozygous Gsα deficiency in MC4R-expressing cells (MC4RGsKO) developed significant obesity with increased food intake and decreased energy expenditure, along with impaired insulin sensitivity and cold-induced thermogenesis. Moreover, the ability of the MC4R agonist melanotan-II (MTII) to stimulate energy expenditure and to inhibit food intake was impaired in MC4RGsKO mice. MTII failed to stimulate the secretion of the anorexigenic hormone peptide YY (PYY) from enteroendocrine L cells, a physiological response mediated by MC4R-Gsα signaling, even though baseline PYY levels were elevated in these mice. In Gsα heterozygotes, mild obesity and reduced energy expenditure were present only in mice with a Gsα deletion on the maternal allele in MC4R-expressing cells, whereas food intake was unaffected. These results demonstrate that Gsα signaling in MC4R-expressing cells is required for controlling energy balance, thermogenesis, and peripheral glucose metabolism. They further indicate that Gsα imprinting in MC4R-expressing cells contributes to obesity in Gsα knockout mice and probably in individuals with Albright hereditary osteodystrophy as well.

Lost in the crowd: identifying targetable MHC class I neoepitopes for cancer immunotherapy.

INTRODUCTION: The recent development of checkpoint blockade immunotherapy for cancer has led to impressive clinical results across multiple tumor types. There is mounting evidence that immune recognition of tumor derived MHC class I (MHC-I) restricted epitopes bearing cancer specific mutations and alterations is a crucial mechanism in successfully triggering immune-mediated tumor rejection. Therapeutic targeting of these cancer specific epitopes (neoepitopes) is emerging as a promising opportunity for the generation of personalized cancer vaccines and adoptive T cell therapies. However, one major obstacle limiting the broader application of neoepitope based therapies is the difficulty of selecting highly immunogenic neoepitopes among the wide array of presented non-immunogenic HLA ligands derived from self-proteins. Areas covered: In this review, we present an overview of the MHC-I processing and presentation pathway, as well as highlight key areas that contribute to the complexity of the associated MHC-I peptidome. We cover recent technological advances that simplify and optimize the identification of targetable neoepitopes for cancer immunotherapeutic applications. Expert commentary: Recent advances in computational modeling, bioinformatics, and mass spectrometry are unlocking the underlying mechanisms governing antigen processing and presentation of tumor-derived neoepitopes.

Genome-Wide Identification of Fitness Factors in Mastitis-Associated Escherichia coli.

Virulence factors of mammary pathogenic Escherichia coli (MPEC) have not been identified, and it is not known how bacterial gene content influences the severity of mastitis. Here, we report a genome-wide identification of genes that contribute to fitness of MPEC under conditions relevant to the natural history of the disease. A highly virulent clinical isolate (M12) was identified that killed Galleria mellonella at low infectious doses and that replicated to high numbers in mouse mammary glands and spread to spleens. Genome sequencing was combined with transposon insertion site sequencing to identify MPEC genes that contribute to growth in unpasteurized whole milk, as well as during G. mellonella and mouse mastitis infections. These analyses show that strain M12 possesses a unique genomic island encoding a group III polysaccharide capsule that greatly enhances virulence in G. mellonella Several genes appear critical for MPEC survival in both G. mellonella and in mice, including those for nutrient-scavenging systems and resistance to cellular stress. Insertions in the ferric dicitrate receptor gene fecA caused significant fitness defects under all conditions (in milk, G. mellonella, and mice). This gene was highly expressed during growth in milk. Targeted deletion of fecA from strain M12 caused attenuation in G. mellonella larvae and reduced growth in unpasteurized cow's milk and lactating mouse mammary glands. Our results confirm that iron scavenging by the ferric dicitrate receptor, which is strongly associated with MPEC strains, is required for MPEC growth and may influence disease severity in mastitis infections.IMPORTANCE Mastitis caused by E. coli inflicts substantial burdens on the health and productivity of dairy animals. Strains causing mastitis may express genes that distinguish them from other E. coli strains and promote infection of mammary glands, but these have not been identified. Using a highly virulent strain, we employed genome-wide mutagenesis and sequencing to discover genes that contribute to mastitis. This extensive data set represents a screen for mastitis-associated E. coli fitness factors and provides the following contributions to the field: (i) global comparison of genes required for different aspects of mastitis infection, (ii) discovery of a unique capsule that contributes to virulence, and (iii) conclusive evidence for the crucial role of iron-scavenging systems in mastitis, particularly the ferric dicitrate transport system. Similar approaches applied to other mastitis-associated strains will uncover conserved targets for prevention or treatment and provide a better understanding of their relationship to other E. coli pathogens.

Seroprevalence and Serointensity of Latent Toxoplasma gondii in a Sample of Elderly Adults With and Without Alzheimer Disease.

INTRODUCTION: Latent infection with Toxoplasma gondii has been associated with behavioral and cognitive changes in animal models and in humans. Early findings have suggested an association between latent toxoplasmosis and Alzheimer disease (AD). On the basis of these factors, we sought to determine whether there is an association between latent toxoplasmosis and AD using a large, well-characterized sample of subjects with AD and age-matched and sex-matched controls without dementia. METHODS: Using ELISA, we determined anti-T. gondii IgG antibody titers in 114 control subjects and in 105 subjects diagnosed with AD through an Alzheimer's Disease Research Center. RESULTS: There were no group differences between groups in age, ethnicity, or sex. Education and socioeconomic status was slightly higher in the control group. Neither the prevalence of anti-T. gondii IgG antibodies (33% in the nondemented control group compared with 41% in the AD group, P=0.25) nor log-transformed antibody concentration (106.6 IU/mL in the control group compared with 140.9 IU/mL in the AD group, P=0.85) differed between the control and AD groups. DISCUSSION: In this sample, we found neither a higher prevalence of latent toxoplasmosis in the AD group compared with the control group nor differences in serum anti-T. gondii IgG titers between groups.

The description of Centrorhynchus globirostris n. sp. (Acanthocephala: Centrorhynchidae) from the pheasant crow, Centropus sinensis (Stephens) in Pakistan, with gene sequence analysis and emendation of the family diagnosis.

A new species of Centrorhynchus (Centrorhynchidae) with receptacle insertion at the posterior third of the proboscis is described from the pheasant crow Centropus sinensis (Stephens) (Cuculidae) in Pakistan. Centrorhynchu sglobirostris n. sp. is similar to the 98 other known species of Centrorhynchus Lühe, 1911 in having long cylindrical trunk with anterior dilation and transverse anastomoses of the secondary lacunar vessels. However, specimens of C. globirostris differ from all other species of the genus by having a unique globular proboscis not divided into anterior proboscis with rooted hooks and posterior proboscis with rootless spines. Posterior hooks of C. globirostris emerge at the level of the receptacle insertion and are uniquely fully rooted. Sequencing and phylogenetic analysis of C. globirostris 18S and 28S ribosomal RNA genes reveals the genetic and evolutionary relationships between C. globirostris and other members of Centrorhynchidae which have representative orthologs in public databases. Comparison to known acanthocephalans confirms appropriate inclusion in the genus Centrorhynchus.

The electrostatic landscape of MHC-peptide binding revealed using inception networks.

Predictive modeling of macromolecular recognition and protein-protein complementarity represents one of the cornerstones of biophysical sciences. However, such models are often hindered by the combinatorial complexity of interactions at the molecular interfaces. Exemplary of this problem is peptide presentation by the highly polymorphic major histocompatibility complex class I (MHC-I) molecule, a principal component of immune recognition. We developed human leukocyte antigen (HLA)-Inception, a deep biophysical convolutional neural network, which integrates molecular electrostatics to capture non-bonded interactions for predicting peptide binding motifs across 5,821 MHC-I alleles. These predictions of generated motifs correlate strongly with experimental peptide binding and presentation data. Beyond molecular interactions, the study demonstrates the application of predicted motifs in analyzing MHC-I allele associations with HIV disease progression and patient response to immune checkpoint inhibitors. A record of this paper's transparent peer review process is included in the supplemental information.

Performance of Endoscopic Sleeve Gastroplasty by Obesity Class in the United States Clinical Setting.

INTRODUCTION: Endoscopic sleeve gastroplasty (ESG) has gained popularity over the past decade and has been adopted in both academic and private institutions globally. We present outcomes of the largest cohort of patients from the United States undergoing ESG and evaluate these according to obesity class. METHODS: We performed a retrospective analysis of adult patients who underwent ESG. Medical information was abstracted from the electronic record with weight records up to 2 years after ESG. Percent total body weight loss (%TBWL) at 6, 12, 18, and 24 months was calculated based on baseline weight at the procedure. SPSS (version 29.0) was used for all statistical analyses. RESULTS: A total of 1,506 patients from 7 sites were included (501 Class I obesity, 546 Class II, and 459 Class III). Baseline demographics differed according to obesity class due to differences in age, body mass index (BMI), height, sex distribution, and race. As early as 6 months post-ESG, mean BMI for each class dropped to the next lower class and remained there through 2 years. %TWBL achieved in the Class III group was significantly greater when compared with other classes at all time points. At 12 months, 83.2% and 60.9% of patients had ≥10% and ≥15% TBWL for all classes. There were no differences in adverse events between classes. DISCUSSION: Real-world data from a large cohort of patients of all BMI classes across the United States shows significant and sustained weight loss with ESG. ESG is safe to perform in a higher obesity class with acceptable midterm efficacy.

Outcomes of concomitant antiobesity medication use with endoscopic sleeve gastroplasty in clinical US settings.

Background: To evaluate the weight loss outcomes of the large US cohort of patients undergoing endoscopic sleeve gastroplasty (ESG) with or without concomitant anti-obesity (AOM) use. Methods: We performed a retrospective analysis of adult patients who underwent ESG from seven different sites, from January 1, 2020 to November 30, 2022. Percent total body weight loss (%TBWL) and %excess weight loss (%EWL) were calculated based on baseline weight at the procedure. Medication use was considered if the subject received a prescribed AOM during the study period. SPSS (version 29.0) was used for statistical analyses. Results: A total of 1506 patients were included (1359 (90.2 %) no AOM use and 147 (9.8 %) AOM use). Patients who were on an active AOM at the time of the procedure had a significantly lower TBWL% as compared to patients not on AOMs at 6 months. At the 24-month visit, patients who were prescribed AOMs after the 12-month visit had a significantly higher TBWL% and EWL% as compared to patients who were on active AOM at the time of the procedure. There was no significant difference between classes of medications at any time point, however, patients on a GLP-1RA had a trend towards improved weight loss at 18 and 24 months. Conclusion: In this large, real-world cohort of patients from the United States, data signal that with the use of pharmacotherapy at the appropriate time, patients can achieve optimal results.

An immunogenetic basis for lung cancer risk.

Cancer risk is influenced by inherited mutations, DNA replication errors, and environmental factors. However, the influence of genetic variation in immunosurveillance on cancer risk is not well understood. Leveraging population-level data from the UK Biobank and FinnGen, we show that heterozygosity at the human leukocyte antigen (HLA)-II loci is associated with reduced lung cancer risk in smokers. Fine-mapping implicated amino acid heterozygosity in the HLA-II peptide binding groove in reduced lung cancer risk, and single-cell analyses showed that smoking drives enrichment of proinflammatory lung macrophages and HLA-II+ epithelial cells. In lung cancer, widespread loss of HLA-II heterozygosity (LOH) favored loss of alleles with larger neopeptide repertoires. Thus, our findings nominate genetic variation in immunosurveillance as a critical risk factor for lung cancer.